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The industrial production of cells has a large unmet need for greater process monitoring, in addition to the standard temperature, pH and oxygen concentration determination. Monitoring the cell health by a vast range of fluorescence cell-based assays can greatly improve the feedback control and thereby ensure optimal cell production, by prolonging the fermentation cycle and increasing the bioreactor output. In this work, we report on the development of a fully automated microfluidic system capable of extracting samples directly from a bioreactor, diluting the sample, staining the cells, and determining the total cell and dead cells concentrations, within a time frame of 10.3 min. The platform consists of custom made stepper motor actuated peristaltic pumps and valves, fluidic interconnections, sample to waste liquid management and image cytometry-based detection. The total concentration of cells is determined by brightfield microscopy, while fluorescence detection is used to detect propidium iodide stained non-viable cells. This method can be incorporated into facilities with bioreactors to monitor the cell concentration and viability during the cultivation process. Here, we demonstrate the microfluidic system performance by monitoring in real time the cell concentration and viability of yeast extracted directly from an in-house made bioreactor. This is the first demonstration of using the Dean drag force, generated due to the implementation of a curved microchannel geometry in conjunction with high flow rates, to promote passive mixing of cell samples and thus homogenization of the diluted cell plug. The autonomous operation of the fluidics furthermore allows implementation of intelligent protocols for administering air bubbles from the bioreactor in the microfluidic system, so that these will be guided away from the imaging region, thereby significantly improving both the robustness of the system and the quality of the data.

We observed strong surface-enhanced Raman scattering on discontinuous nanostructured aluminum films using 785 nm excitation even though dielectric constants of this metal suggest plasmon supported spectroscopy in the ultraviolet range. The excitation of SERS correlates with plasmon resonances in the 1.3-2.5 eV range identified in electron energy loss spectra.

The objective of this article is to provide an overview and critical evaluation of the use of carbon nanotubes and related carbon-based nanomaterials for microchip chromatography. The unique properties of carbon nanotubes, such as a very high surface area and intriguing adsorptive behaviour, have already been demonstrated in more classical formats, for improved separation performance in gas and liquid chromatography, and for unique applications in solid phase extraction. Carbon nanotubes are now also entering the field of microfluidics, where there is a large potential to be able to provide integrated, tailor-made nanotube columns by means of catalytic growth of the nanotubes inside the fluidic channels. An evaluation of the different implementations of carbon nanotubes and related carbon-based nanomaterials for microfluidic chromatography devices is given in terms of separation performance and ease of fabrication.

Electrically insulated carbon nanotube (CNT) based separation columns have been fabricated that can withstand an electrical field strength of more than 2.0 kV cm(-1) without bubble formation from electrolysis. The carbon nanotubes were grown in a pillar array defined by photolithographic patterning of the catalyst layer used for synthesis of the nanotubes. Multiwall carbon nanotubes are inherently electrically conductive and cannot be used as a continuous layer in the microfluidic channels, without short circuiting the electrical field in the separation column, when the field strength is more than a couple of 100 V cm(-1). Here, the carbon nanotubes are grown in an array of hexagonal pillars, where the nanotubes in the individual pillars are not in direct electrical contact with the nanotubes of the adjacent pillars. This makes it possible to increase the electrical field strength from around 100 V cm(-1) to more than 2.0 kV cm(-1) and thereby to use the CNT columns for electrokinetic separations with the high electrical field strengths that are typically used in this application. An electrochromatographic separation of two Coumarin dyes was demonstrated on the CNT column with an acetonitrile content of 90%.

Taking the next step from individual functional components to higher integrated devices, we present a feasibility study of a lab-on-a-chip system with five different components monolithically integrated on one substrate. These five components represent three main domains of microchip technology: optics, fluidics and electronics. In particular, this device includes an on-chip optically pumped liquid dye laser, waveguides and fluidic channels with passive diffusive mixers, all defined in one layer of SU-8 polymer, as well as embedded photodiodes in the silicon substrate. The dye laser emits light at 576 nm, which is directly coupled into five waveguides that bring the light to five different locations along a fluidic channel for absorbance measurements. The transmitted portion of the light is collected at the other side of this cuvette, again by waveguides, and finally detected by the photodiodes. Electrical read-out is accomplished by integrated metal connectors. To our knowledge, this is the first time that integration of all these components has been demonstrated.

Electrically insulated porous SiO2 channels for electrokinetic separation devices were fabricated based on a mask-less etching process for creation of high aspect ratio needles in silicon. The silicon needles are converted to SiO2 by oxidation and integrated within the interior of a fluidic channel network. The channels are about 5 microm high with a pore size of 0.5+/-0.2 microm. An electrophoretic separation of a mixture of fluorescein and 5-carboxyfluorescein using epi-fluorescence detection was performed to verify proper electrokinetic transport in the porous channels. The plate height was about 170,000 m-1 for a field strength of 170 V cm-1. In the near future, it is intended to extend the fabrication scheme to include an array of porous pillars for capillary electrochromatography experiments.

Flow cytometry is widely used for analyzing microparticles, such as cells and bacteria. In this paper, we report an innovative microsystem, in which several different optical elements (waveguides, lens and fiber-to-waveguide couplers) are integrated with microfluidic channels to form a complete microchip flow cytometer. All the optical elements, the microfluidic system, and the fiber-to-waveguide couplers were defined in one layer of polymer (SU-8, negative photoresist) by standard photolithography. With only a single mask procedure required, all the fabrication and packaging processes can be finished in one day. Polystyrene beads were measured in the microchip flow cytometer, and three signals (forward scattering, large angle scattering and extinction) were measured simultaneously for each bead. To our knowledge this is the first time forward scattered light and incident light extinction were measured in a microsystem using integrated optics. The microsystem can be applied for analyzing different kinds of particles and cells, and can easily be integrated with other microfluidic components.